Koch A E, Kunkel S L, Harlow L A, Johnson B, Evanoff H L, Haines G K, Burdick M D, Pope R M, Strieter R M
Department of Medicine, Northwestern University Medical School, Chicago, Illinois 60611.
J Clin Invest. 1992 Sep;90(3):772-9. doi: 10.1172/JCI115950.
Cells within the synovial tissue may recruit mononuclear phagocytes into the synovial fluid and tissues of arthritic patients. We investigated the production of the chemotactic cytokine monocyte chemoattractant protein-1 (MCP-1) using sera, synovial fluid, synovial tissue, as well as macrophages and fibroblasts isolated from synovial tissues from 80 arthritic patients. MCP-1 levels were significantly higher (P less than 0.05) in synovial fluid from RA patients (mean 25.5 +/- 8.1 ng/ml [SE]) compared to synovial fluid from osteoarthritis (OA) patients (0.92 +/- 0.08), or from patients with other arthritides (2.9 +/- 1.5). MCP-1 levels in RA sera (8.44 +/- 2.33) were significantly greater than MCP-1 in normal sera (0.16 +/- 0.06). The quantities of RA synovial fluid IL-8, which is chemotactic for neutrophils and lymphocytes, and MCP-1 were strongly positively correlated (P less than 0.05). To examine the cellular source of MCP-1, RA synovial tissue macrophages and fibroblasts were isolated. Synovial tissue fibroblasts did not express MCP-1 mRNA, but could be induced to produce MCP-1 by stimulation with either IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), or LPS. In contrast, unlike normal peripheral blood monocytes or alveolar macrophages, RA synovial tissue macrophages constitutively expressed MCP-1 mRNA and antigen. Immunohistochemical analysis of synovial tissue showed that a significantly greater percentage of RA macrophages (50 +/- 8%) as compared to either OA macrophages (5 +/- 2) or normal macrophages (1 +/- 0.3) reacted with anti-MCP-1 antibodies. In addition, the synovial lining layer reacted with MCP-1 in both RA and OA synovial tissues. In contrast, only a minority of synovial fibroblasts (18 +/- 8%) from RA synovium were positive for immunolocalization of MCP-1. These results suggest that synovial production of MCP-1 may play an important role in the recruitment of mononuclear phagocytes during inflammation associated with RA and that synovial tissue macrophages are the dominant source of this cytokine.
滑膜组织中的细胞可能会将单核吞噬细胞招募到关节炎患者的滑液和组织中。我们使用血清、滑液、滑膜组织，以及从80例关节炎患者的滑膜组织中分离出的巨噬细胞和成纤维细胞，研究了趋化细胞因子单核细胞趋化蛋白-1（MCP-1）的产生情况。与骨关节炎（OA）患者（0.92±0.08）或其他关节炎患者（2.9±1.5）的滑液相比，类风湿关节炎（RA）患者滑液中的MCP-1水平显著更高（P<0.05）（平均25.5±8.1 ng/ml[标准误]）。RA血清中的MCP-1水平（8.44±2.33）显著高于正常血清中的MCP-1水平（0.16±0.06）。对中性粒细胞和淋巴细胞具有趋化作用的RA滑液白细胞介素-8（IL-8）与MCP-1的含量呈强正相关（P<0.05）。为了研究MCP-1的细胞来源，分离了RA滑膜组织巨噬细胞和成纤维细胞。滑膜组织成纤维细胞不表达MCP-1 mRNA，但可通过白细胞介素-1β、肿瘤坏死因子-α（TNF-α）或脂多糖刺激诱导产生MCP-1。相比之下，与正常外周血单核细胞或肺泡巨噬细胞不同，RA滑膜组织巨噬细胞组成性表达MCP-1 mRNA和抗原。滑膜组织的免疫组织化学分析表明，与OA巨噬细胞（5±2）或正常巨噬细胞（1±0.3）相比，RA巨噬细胞与抗MCP-1抗体反应的比例显著更高（50±8%）。此外，在RA和OA滑膜组织中，滑膜衬里层均与MCP-1发生反应。相比之下，RA滑膜中只有少数滑膜成纤维细胞（18±8%）MCP-1免疫定位呈阳性。这些结果表明，滑膜产生MCP-1可能在与RA相关的炎症过程中单核吞噬细胞的招募中起重要作用，并且滑膜组织巨噬细胞是这种细胞因子的主要来源。
